Research Overview: Cannabis and Autoimmune Disorders

Since autoimmune disease involves malfunction of the immune system, the same research on cannabis and immune system disorders applies to autoimmune disease. And as with more traditional treatments for autoimmune disease, cannabis tends to address immune system disorders by decreasing inflammation and swelling.

Immune System Basics

Autoimmune disorders occur when our immune systems malfunction. To understand autoimmune disorders, we must, therefore, first understand how the immune system works.

Antigens Generate Antibodies

Our immune systems are responsible for protecting our bodies from anything harmful, whether coming from outside our bodies or from within. To do this, our immune systems must be able to distinguish between self and non-self. An antigen is any molecule that our immune systems recognize as being non-self. Our bodies are pre-programmed to recognize thousands of different antigens, and they also learn to designate additional molecules as antigens based on experience. When our immune system identifies a molecule in our body as an antigen, it tags it with a unique identifier called an antibody. The antibody signals to the rest of the immune system that the antigen is a non-self-molecule, so it can be destroyed (1). The presence of antibodies tagged to antigens triggers a response by our immune systems, which generates white blood cells (“lymphocytes”) of varying types to kill the antigens and remove them from our bodies (2).

Cell Damage Induces Inflammation

Inflammation is an immune system response to the presence of viruses, bacteria, injuries, or other sources that damage our cells. During the inflammation process, blood vessels dilate and become permeable, enabling white blood cells and other harm-fighting agents to flow to the area of injury. The dilated blood vessels cause heat and redness, the flood of white blood cells into the area causes swelling, and other immune system agents increase sensitivity to pain. Once the pathogens have been neutralized, our immune systems clean up the debris then repair any damage, restoring our bodies to normal (3).

Autoimmune Disease Basics

Autoimmune disease occurs when the body mistakes self for non-self: our immune systems mistake specific molecules from our own body’s organs and tissues as being toxic antigens. Our immune systems then respond accordingly, by tagging the antigens with antibodies and mounting attacks on those cells. Since the molecules mistaken for toxic antigens are generated by normal–that is, ongoing–bodily functions, the attacks by our immune systems on our own cells becomes a persistent process (4).

Autoimmune disease is not well-understood by the medical community. It is thought to involve both genes and environment. Specifically, genetic and environmental phenomena increase the reactivity of our immune systems, making it easier for our bodies to mistake benign molecules for toxins (4).

Autoimmune disease occurs in about 3-6% of the population; it is more common in females and specific forms of the disease are more common in particular ethnic groups. Since the incidence of autoimmune disease has been increasing, it suggests environmental factors, including overexposure to chemicals, a Western diet, or underexposure to germs (that is, excessively antiseptic environments), contribute to its development (5).

Common forms of autoimmune disease include, for example (5):

• Rheumatoid arthritis (RA): The immune system attacks joints, causing joint soreness and stiffness.
• Multiple sclerosis (MS): The immune system attacks the insulation (that is, myelin sheath) that protects nerve fibers and enables the smooth flow of signaling between the brain, spinal cord, and the rest of the body.
• Inflammatory bowel disease (IBD): The immune system attacks the lining of the intestinal wall, causing digestive problems.

Essentially, autoimmune disease involves hyperactivity of the immune system. This hyperactivity causes two sets of problems. First, as the immune system attacks cells from a patient’s own body, it causes damage to the affected areas. The direct damage then causes problems with interconnected activities. For example, in the case of multiple sclerosis, the immune system attacks myelin sheaths on nerve fibers. This impedes signaling between the brain, spinal cord, and the rest of the body, leading to problems such as limb numbness, tremors, and pain.

The second set of problems caused by autoimmune disease is collateral damage to nearby cells and tissues associated with the ongoing swelling and irritation of the immune system.

There are no cures for autoimmune disease. There are, however, treatments that focus on reducing immune system activity (that is, immunosuppressants), such as painkillers, anti-inflammatories, cortisone pills, and creams (5).

Research on Cannabis and Autoimmune Disease

Since autoimmune disease involves malfunction of the immune system, the same research on cannabis and immune system disorders applies to autoimmune disease. As with more traditional treatments for autoimmune disease, cannabis tends to address immune system disorders by decreasing inflammation and swelling.

Mechanisms of Action

There are a host of in vitro and in vivo studies examining how cannabis works to treat the symptoms and causes of autoimmune disease.

Autoimmune Disease Generally

Let’s start with cannabis’s mechanisms of actions (MoAs) for autoimmune disease generally. The primary way cannabinoids influence cells is by binding to receptors that are located on cell surfaces, thereby inducing activity. Cannabinoid type 2 receptors (CB2) are densely located on all different types of immune system cells. Generally speaking, then, cannabis helps treat autoimmune disorders by binding to cannabinoid receptors on immune system cells, causing decreases in immune system activity. Four immunosuppressive mechanisms of action in particular enable cannabis to relieve symptoms from autoimmune disorders.

1. Induce cell death: Apoptosis is a natural process used by the body to rid itself of unneeded or abnormal cells. Cannabinoids induce apoptosis in white blood cells involved in the inflammation process (that is, killer T cells), thus alleviating the inflammatory response (6-8).
2. Inhibit cell proliferation: Cell proliferation is the speed at which cells replicate themselves. Cannabinoids inhibit cell proliferation in white blood cells involved in the inflammation process (that is, killer T cells, B cells), thus alleviating the inflammatory response (6-9).
3. Suppress cytokine production: Cytokines are part of the entourage of immune system cells; one of their functions is to help either amplify or limit inflammatory responses. Autoimmune disease may cause malfunctions in the immune system that cause long-term production of pro-inflammatory cytokines (7). Cannabinoids suppress cytokine production, thus alleviating the inflammatory response (6,7,9,10).
4. Induce regulatory T cell production: Finally, cannabinoids induce production of white blood cells that suppress the cytokine production (that is, regulatory T cells), thus mitigating inflammatory responses associated with autoimmune disease (7,8,11).

Specific Autoimmune Diseases

Aside from addressing general autoimmune dysfunction, studies have also established cannabis’s MoAs for addressing specific autoimmune diseases.

Crohn’s disease and IBD: Studies have shown that the endocannabinoid system regulates intestinal inflammation (6) and intestinal motility (movement of substances through the gastrointestinal tract) (12).

Multiple sclerosis: Studies have shown that cannabis may inhibit the inflammatory response in MS that contributes to the destruction of myelin and myelin-producing cells. By inhibiting these inflammatory responses, cannabis mitigates MS-induced bladder control problems, pain, spasticity, and tremors (13).

Rheumatoid arthritis: Studies have shown that cannabis inhibits progression and proliferation of RA generally by inducing cell death that reduces bone tissue degeneration (7). Studies have also shown that cannabinoid receptors are located in the synovia, that is the fluid-filled cavities, which keep bones together and permit free bone movement. In the synovia, cannabinoids prevent the progression of RA by reducing synovial inflammation and bone destruction (6).

Clinical Studies

Crohn’s Disease and IBD

One large-scale retrospective study of patients with Crohn’s Disease (14) and several other much smaller studies concluded that patients found substantial improvements in their symptoms after using cannabis.

MS

MS is one of the most-studied diseases for cannabis treatment. Dozens of clinical studies, including a good number of moderately-sized randomized controlled trials, have found that cannabis may improve MS-related bladder control problems, pain, spasticity, and tremor.

RA

“There are currently no randomized clinical trials investigating the use of cannabis in the treatment of RA, partly because of the availability of effective biological anti-inflammatory agents in the therapeutic armamentarium. However, one preliminary randomized, placebo-controlled study has assessed the efficacy, tolerability and safety of five weeks’ treatment with a synthetic tetrahydrocannabinol (THC) analogue in 58 RA patients and found that pain was significantly reduced and disease activity significantly suppressed” (6).

Issues of Note

Several issues noted by researchers about cannabis and autoimmune disease are worth mentioning.

Cannabis Treatment for Autoimmune Disease Must Be Personalized

“As each autoimmune disease differ [sic] in symptoms, it also differs in the ‘culpable’ immune cells and cytokines inciting the disease. Hence, declaring that cannabis treatment is beneficial for autoimmune diseases does not suffice, and treatment options should be tailored for each disease.” Furthermore, since each person’s body chemistry and endocannabinoid system are unique, “cannabis or cannabinoid treatment should possibly be tailored not only per disease but also per person,” (6).

Biphasic Effects

Cannabinoids are known to exhibit biphasic effects, that is, low doses can generate one effect in patients while higher doses exhibit the opposite effect. For example, studies have shown that low doses of THC may decrease anxiety, while higher doses may increase anxiety (15).

These same biphasic effects have been found for cannabis’s effects on the production of white blood cells: low doses of cannabinoids may stimulate the production of white blood cells (T cells, B cells, and cytokines), while higher doses may decrease production (7-9).

Promotes Infection by Suppressing the Immune System

The discussion thus far has noted the ability of cannabis to suppresses immune system activity. This suppression helps reduce hyperactive immune systems in patients with autoimmune disease, thereby providing relief. At the same time, however, we must recognize that a primary role of the immune system is to fight off infections. In this sense, then, using cannabis to suppress immune system activity to help with autoimmune disease may inadvertently increase patients’ susceptibility to infections (8).

References

1. Antibody and antigen (n.d.). Science Clarified. Retrieved from http://www.scienceclarified.com/Al-As/Antibody-and-Antigen.html.
2. S. Dutta, (2021, Mar 16). News-Medical. Retrieved from https://www.news-medical.net/life-sciences/What-is-an-Ant?”igen.aspx.
3. Immune response (n.d.). Medline Plus. Retrieved from https://medlineplus.gov/ency/article/000821.htm.
4. P. Marrack, J. Kappler, and B.L. Kotzin, Nature Medicine 7(8), 899–905 (2001). https://doi.org/10.1038/90935.
5. S. Watson, Healthline (2019, Mar 26). Retrieved from https://www.healthline.com/health/autoimmune-disorders.
6. V. Giorgi, D. Marotto, A. Batticciotto, F. Atzeni, S. Bongiovanni, and P. Sarzi-Puttini, ImmunoTargets and Therapy 10, 261–271 (2021). https://doi.org/10.2147/ITT.S267905.
7. P. Nagarkatti, R. Pandey, S.A. Rieder, V.L. Hegde, and M. Nagarkatti, Future Medicinal Chemistry 1(7), 1333–1349 (2009). https://doi.org/10.4155/fmc.09.93.
8. V. Katchan, P. David, and Y. Shoenfeld, Autoimmunity Reviews (2016, Feb). Retrieved from https://pubmed.ncbi.nlm.nih.gov/26876387/.
9. P. Massi, et al., Current Pharmaceutical Design (2006). Retrieved from https://pubmed.ncbi.nlm.nih.gov/16918439/.
10. Cytokines and inflammation (n.d.). Abcam. Retrieved from https://www.abcam.com/research-areas/cytokines-and-inflammation.
11. A. Oláh, et al., Frontiers in Immunology (2017, Nov 10). Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2017.01487/full.
12. M. Pesce, et al., J Cell Mol Med (2018, Feb). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783846/.
13. A. Malfitano and M. Bifulco, Current Drug Targets - CNS & Neurological Disorders (2006, Jan). Retrieved from https://www.researchgate.net/publication/7394957.
14. C. Bifulco, et al., Digestive Diseases and Sciences (2019). Retrieved from https://link.springer.com/article/10.1007/s10620-019-05556-z.
15. L. Sharpe, et al, J. Transl. Med. (2020, Oct 2). Retrieved from https://pubmed.ncbi.nlm.nih.gov/33008420/.

About the Author

Ruth Fisher, PhD, is a systems design researcher and analyst. She analyzes markets to determine how environments shape outcomes. She is co-founder of CannDynamics, and author of The Medical Cannabis Primer and Winning the Hardware-Software Game: Using Game Theory to Optimize the Pace of New Technology Adoption. Dr. Fisher has worked in the technology and healthcare sectors on behalf of technology companies, early-stage researchers, physicians, and technology start-ups.